OBJECTIVES/GOALS: Vaginal delivery is typically avoided in extremely preterm breech fetuses due to the concern for head entrapment by the cervix. Development of a device to prevent head entrapment would be best addressed by a multidisciplinary approach incorporating engineering principles with clinical obstetrics. METHODS/STUDY POPULATION: Construction of a collaborative multidisciplinary team to address the clinical challenge of preventing head entrapment was initiated through a unique course at the Massachusetts Institute of Technology (Course 2.75, Medical Device Design). The course would provide a structured means by which students (senior undergraduate and graduate students in Mechanical Engineering) would be paired with a clinical advisor and faculty in their department. Weekly team meetings were scheduled to review the clinical context pertinent to the problem and review engineering principles needed to develop a solution. The course also provided a small monetary budget ($4K) for the students to purchase supplies. RESULTS/ANTICIPATED RESULTS: During the semester long course, several iterations of a prototype were designed. Each subsequent rendition was evaluated from both an engineering and manufacturing perspective, as well as clinical appropriateness. The weekly meetings allowed for rapid re-design and assured that all necessary parameters were considered by the entire team. Students also had access to lab facilities and additional mentorship that allowed for supplementary input beyond that generated by core team members. These interactions, along with those of their classmates working on other projects, provided a strong base for exploring subsequent device development. DISCUSSION/SIGNIFICANCE OF IMPACT: Successful medical device development requires a collaborative process and students can be ideal members of these teams as they reside in an environment that is conducive to exploration and novel idea generation. Course-based student led team science platforms can provide an excellent foundation for solving uniquely challenging medical problems.

OBJECTIVES/GOALS: Food and Drug Administration (FDA) warning letters regarding misbranding of products intended to treat, prevent, or diagnose COVID-19 were used as a proxy for assessing misinformation on social media. The FDA database of Warning Letters was used to identify the largest misinformation contributor. METHODS/STUDY POPULATION: On November 9, 2022, the full dataset of warning letters dating back to January 1, 2018 was extracted from the FDA website. Separate datasets were also extracted using the search terms: Facebook’, Twitter’, YouTube’, and Instagram’. The data entries were organized by issuing office and subject. The subjects were then filtered to only include letters related to misbranding of products for COVID-19. Letters regarding medical devices, manufacturing practices, and adulterated products were excluded from the analysis. Cumulative totals were collected for the number of letters issued for each search term. These totals were stratified by year and scaled by platform size for relative comparison. RESULTS/ANTICIPATED RESULTS: The FDA’s Center for Drug Evaluation and Research issued the most letters related to misbranding of COVID-19 products, 153 out of the 2798 entries in the complete dataset. Analysis of the datasets by search term show: 53, 18, 24, and 17 letters were related to Facebook, Twitter, YouTube, and Instagram respectively. Forty-one letters were related to other non-social media sources. Facebook had the most letters issued, however when scaled to account for the size of each respective platform’s approximate user base, Twitter had the largest proportional amount of misinformation regarding agents for the management of COVID-19, followed by Facebook, then Instagram. Most letters were issued in 2020. DISCUSSION/SIGNIFICANCE: In light of COVID-19, many social media sites adopted policies to limit inaccurate information. The success of these efforts have been variable. Although Facebook is the largest absolute contributor assessed, greater attention should be given to the policies of other platforms utilized by the industry.

ABSTRACT IMPACT: This work will estimate current EPT implementation in Minnesota and provide cost-effectiveness analyses of different implementation scenarios to inform STI treatment policy. OBJECTIVES/GOALS: This research aims to 1) assess current implementation of Expedited Partner Therapy (EPT) as treatment for C. Trachomatis (chlamydia) and N. Gonorrhoeae (gonorrhea) among healthcare providers in Minnesota and to 2) simulate the current burden of chlamydia and gonorrhea infections to test the cost-effectiveness of increasing EPT implementation. METHODS/STUDY POPULATION: We will conduct key informant interviews (KII) and an online survey of health providers across the continuum of care for chlamydia and gonorrhea treatment. Based on experience in prior studies, the KII sample size is expected to be about 15 informants. KIIs will be carried out among providers who submitted EPT protocols to the Minnesota Department of Health to understand how EPT is currently being implemented. KII results will inform the online survey of health providers, which will estimate how many providers across the state provide EPT. We will distribute the survey through Minnesota health provider networks to achieve a sample of at least 500 health providers. The KII and survey results will inform model structure and parameter values for a compartmental cost-effectiveness model of EPT. RESULTS/ANTICIPATED RESULTS: Initial results from KII pilots suggest that EPT is primarily provided through a paper script for the sexual partner of a patient who tests positive for CT or NG by the treating provider. Less commonly, a patient’s partner who is already a patient in the health system may receive notification and treatment through the provider. While EPT is legal in Minnesota, concerns about medical liability for adverse reactions and difficulty obtaining paper scripts in electronic workflows are barriers to implementation. The statewide survey will include questions to estimate the likelihood of EPT provision among providers when these concerns are addressed. These figures will be integrated into the cost-effectiveness model to simulate outcomes and costs across different EPT implementation scenarios. DISCUSSION/SIGNIFICANCE OF FINDINGS: The statewide survey will define cost-effectiveness model parameters, including the proportion of providers in the state who currently provide EPT or would be willing to provide EPT under different scenarios. Study findings will be shared with health provider networks and health departments to inform STI treatment procedures and state EPT policies.

Objectives/Goals: Ventilator-associated pneumonia (VAP) is an infection caused by bacteria, viruses, or fungi during mechanical ventilation. We analyzed a cohort of COVID-19 patients admitted to the intensive care unit with respiratory failure with different VAP outcomes. We hypothesize that the multiomics data can help predict VAP development within this cohort. Methods/Study Population: We recruited participants from a cohort on a NYU IRB protocol (i22–00616), who had COVID19 respiratory failure, admitted to ICU, and required invasive mechanical ventilation (n = 245). We collected and analyzed research specimens (bronchoalveolar lavage [BAL, n = 213], tracheal aspirates [n = 246], background [n = 18]) and clinical cultures (sputum and BAL) for 245 participants. A panel of experts adjudicated VAP within the cohort, resulting in 92 VAP diagnoses. We annotated metatranscriptome (Illumina NovaSeq) using a Kraken/Bracken database, and KEGG for functional annotation of transcriptome data (Illumina HiSeq). We used edgeR (v.4.0.16) to analyze differential expression of metatranscriptome and transcriptome data. Results/Anticipated Results: We diagnosed VAP in n = 92 (38%) participants. We found significant differences in days of overall hospital stay (p Discussion/Significance of Impact: VAP is a serious complication of mechanical ventilation, and oral commensals alter the lung microbiome and host immunity. We identified a transcriptome-metatranscriptome signature that identifies those at VAP risk. VAP was associate with both pro- and anti-inflammatory gene expression resulting in increased risk for lower airway infection.

Objectives/Goals: Opioids treat pain but with the risk of severe adverse effects. The opioid positive allosteric modulator BMS-122 has been shown to enhance opioid antinociception in animal models without increasing adverse effects. However, whether BMS-122 is effective in chronic neuropathic pain is unknown. Methods/Study Population: We used two animal models: spared nerve injury (SNI) and tibial neuroma. Injuries were performed on male and female Sprague-Dawley rats. Animals developed robust sensitivity to tactile stimulation similar to that seen in patients. Animals with SNI received the mu-opioids methadone, morphine, and buprenorphine, or gabapentin (30 mg/kg, s.c.), with or without BMS-122 (10 mg/kg, s.c.). Tactile hypersensitivity was measured using von Frey filaments. Animals with tibial neuroma received methadone (s.c.) with or without BMS-122 (10mg/kg s.c.), and tactile hypersensitivity was measured using a modified Tinel’s test, in which the neuroma was directly stimulated. Results/Anticipated Results: Hypersensitivity following SNI was reversed with administration of high-dose opioids or gabapentin. Following pre-treatment with BMS-122 low, ineffective doses of opioid or gabapentin significantly reversed the hypersensitivity. Buprenorphine was unable to fully reverse the hypersensitivity alone but was fully efficacious in the presence of BMS-122. Animals with tibial neuroma developed hypersensitivity at the neuroma site, but the doses of methadone required to reverse this sensitivity also induced respiratory depression. In the presence of BMS-122, a low, non-effective, dose of methadone reversed hypersensitivity without depressing breathing. No sex differences were observed in either condition. Discussion/Significance of Impact: These data show that positive allosteric modulators like BMS-122 provide an opioid-sparing effect in chronic neuropathic pain. Furthermore, BMS-122 appears to enhance endogenous opioid peptides to increase the effectiveness of non-opioid analgesics. Overall, these data support the continued development of modulators as therapeutics.

ABSTRACT IMPACT: Our work may be able to impact the examination and clinical decision making of a clinician to identify and target movement impairments to treat people with low back pain. OBJECTIVES/GOALS: Test if the magnitude of spinal control impairments is different in two clinical tests of lower limb movement in people with and without low back pain (LBP). The impairment is defined as the time difference between the start of limb to lumbopelvic motion. Also, test if the magnitude of impairments across tests is associated with LBP intensity and function. METHODS/STUDY POPULATION: 18 controls and 21 people with LBP (51.6% F, 34.5 ±11.5 yrs) participated in a cross-sectional, laboratory-based study. Subjects completed the modified Oswestry Disability Questionnaire (LBP-related functional limitation measure; 0-100%) and the Numeric Pain Rating Scale (LBP intensity; average pain prior 7 days; 0-10) self-report surveys and clinical tests of hip medial and lateral rotation performed in prone. A three-dimensional motion capture system was used to capture angular lumbopelvic and hip motion across time. A 2x2 mixed model ANOVA will be used to examine the effects of group, hip rotation test, and group x hip rotation test. Separate bivariate correlations will be used to quantify the association of magnitude of the impairment to (1) average LBP intensity and (2) LBP-related functional limitation. RESULTS/ANTICIPATED RESULTS: We hypothesize that, compared to healthy controls, people with LBP will display a greater magnitude of impairment across the hip medial and lateral rotation tests. In addition, we hypothesize that the magnitude of the difference in impairment between people with LBP vs controls will be larger during the hip lateral rotation test compared to the hip medial rotation test. Finally, we hypothesize that in people with LBP the magnitude of the impairments across tests will be associated with LBP intensity and LBP-related functional limitation. DISCUSSION/SIGNIFICANCE OF FINDINGS: If our hypotheses are supported, the hip rotation tests would further be recognized as a key part of a clinician’s examination and an important target for treatment of LBP.

OBJECTIVES/SPECIFIC AIMS: To analyze contemporary study design methods and clinical trial approaches in placebo research. METHODS/STUDY POPULATION: An analysis was conducted on the following studies: I. “Managing” the Placebo Effect: The Single-Blind Placebo Lead-in Response in Two Pain Models by RN Haden, et al. The objective of the study was to consider elements of the placebo response in the context of two pain models using a “single-blind placebo lead-in” design (SBPLI) by engaging the “placebo response” prior to randomization to active drug and placebo-controlled conditions. The methods of the study included two pilot drug trials using knee osteoarthritis (KOA) and non-radicular low back pain (LBP) subjects, SBPLI protocols were conducted. In the first study, 36 subjects with non-radicular CLBP were enrolled in a double-blind, randomized, placebo-controlled trial of hydromorphone ER. In the second study, a total of 42 subjects with chronic KOA pain were enrolled in a double-blind, randomized, placebo-controlled study of milnacipran. Gender and/or diagnosis affected placebo responses as observed in changes in patient self-reported pain, depressive and pain anxiety symptoms were examined. Additionally, the placebo response on performance-based tests (stair climbing, range of motion (ROM), sit to stand repetitions, and 6-minute treadmill distance) was evaluated. II. Randomized Placebo-Controlled Placebo Trial to Determine the Placebo Effect Size by L. Gerdesmeyer, et al. The objective of the study was to analyze the pure placebo effect on clinical, chronic pain through a blinded RCT. The methods of the study included 182 patients suffering from chronic plantar heel pain for over 6 months, who failed to respond to conservative treatments, were screened and 106 of these patients were enrolled into this study. The patients were randomly assigned to receive either a blinded placebo shockwave treatment or an unblinded placebo shockwave treatment. The primary outcome measure was the differences in percentage change of visual analogue scale (VAS) scores 6 weeks after the intervention. The secondary outcome measure was the differences in Roles and Maudsley pain score (RMS) 6 weeks after intervention. III. Open-label placebo treatment in chronic low back pain: a randomized controlled trial by C. Carvalho, et al. The objective of the study was to investigate whether placebo effects in chronic low back pain could be harnessed ethically by adding open-label placebo (OLP) treatment to treatment as usual (TAU) for 3 weeks. The methods of the study included 97 randomized participants in a 3-week randomized control trial comparing current treatment plus OLP to current treatment alone (TAU). RESULTS/ANTICIPATED RESULTS: N/a DISCUSSION/SIGNIFICANCE OF IMPACT: The aforementioned studies provide placebo researchers with contemporary and reliable methodologies to examine placebo effects on participants. These methodologies provide scientists with clinical translational research methodology styles based on the foundation of regulatory science.

Objectives/Goals: The WF DICQI team uses targeted messaging across many platforms to inform investigators across the Advocate Health (AH) enterprise of available programs and services, turning research into action. Translational science is valued at Wake Forest University School of Medicine, the academic core of AH. Methods/Study Population: The DICQI team partners with all Wake Forest CTSI teams to create tailored communication and dissemination plans for their resources and initiatives, designed to help investigators translate research into practice. Participants include program leaders, staff, and high users of CTSI services. Efforts focus on interviewing previous program participants and producing related articles, alongside developing targeted plain language messaging for internal newsletters, social media, and providing customized flyers and email content. This initiative enhances awareness among investigators along with driving engagement and collaboration. Results/Anticipated Results: These dissemination strategies motive investigators to use CTSI resources and engage in continuous learning. An increase in CTSI service usage is expected after implementing the dissemination plans. Plain language messaging and visually appealing graphics make scientific findings more accessible to a broader audience, so increased engagement on social media is also anticipated. These efforts make it easier for readers to understand research findings, apply them, and encourage collaboration. We will work with more AH centers and programs to create tailored plans and amplify the impact of WF CTSI. We plan to share our approach with other institutions, fostering collaboration nationwide. Discussion/Significance of Impact: The WF CTSI DICQI’s dissemination efforts are designed to increase awareness and utilization of available resources, which will drive more robust research from investigators, and more engagement from a broader audience, bridging practice–research collaboration across the AH enterprise.

OBJECTIVES/GOALS: Reveal common immune mechanisms in dysregulated age-related lobular involution (ARLI) and post-partum lobular involution (PPLI) to understand their link to increased breast cancer risk, challenging the traditional view of their distinctiveness. Ultimately, to improve breast cancer risk assessment and personalized prevention METHODS/STUDY POPULATION: The Mayo Clinic Benign Breast Disease (BBD) cohort comprises of ~20,000 women with benign biopsies, including ~1000 women with sequential benign biopsies. Lobular involution (LI) status was assessed by selecting perimenopausal women, ages 45-55, with sequential biopsies, comparing acini number and lobule size between initial and subsequent biopsies. NanoString IO360/ BC360 RNA profiling identified differentially expressed genes associated with dysregulated LI. Using multiplex immunofluorescence (mIF), I'll analyze and spatially map immune biomarkers related to dysregulated ARLI and PPLI in BBD tissue from perimenopausal women who did or did not go on to develop breast cancer, assessing the commonality of ARLI and PPLI markers and exploring their potential as risk biomarkers for breast cancer. RESULTS/ANTICIPATED RESULTS: Preliminary findings link patients who display dysregulated ARLI with an increased breast cancer risk and identify vital PPLI biomarkers in perimenopausal women. I expect the biopsies of women who developed post-menopausal breast cancer (PMBC) and post-partum breast cancer (PPBC) to exhibit elevated levels of dysregulated ARLI immune biomarkers and PPLI biomarkers. Spatially mapping these markers promises to provide a more comprehensive understanding of their interactions, potentially revealing common immunological pathways. These findings could transform our current paradigm of ARLI and PPLI as distinct processes and demonstrate their interconnection in shaping breast cancer risk. DISCUSSION/SIGNIFICANCE: PMBC and PPBC dominate majority of breast cancer cases. Both involve activation of the understudied process of lobular involution, which has been shown to have pro-tumorigenic traits. Elucidating these mechanisms will aid more efficient risk stratification and personalized prevention to reduce incidence and mortality of breast cancer.

Objectives/Goals: We aim to develop an intuitive interface to understand the possible relationships between data from different RNA-Seq technologies. It can help novice users and educators to understand, analyze, explain, and visualize such datasets from diverse platforms, all without the need for additional software installations or strong programming expertise. Methods/Study Population: An online interactive interface is developed, integrating robust algorithms for three distinct types of analyses: DESeq2 for bulk RNA-seq, CIBERSORTx for deconvolution, and Seurat for single-cell analysis, with plans to include more algorithms. It allows a demo mode for training using the sample datasets and option for tailored analysis using user’s partially processed data. The interface provides capability to process bulk RNA-seq data from raw counts or a differential gene list. Further, deconvolution analysis for bulk RNA-seq data can be done using raw counts and single-cell data analysis can be performed using processed sequence reads, organized into three key files: barcodes, matrix, and features. Users also have an option to download the results as a zipped file, for samples from human and mouse studies. Results/Anticipated Results: Users with an active internet connection can access the interface from any major web browser. They can adjust parameters – such as genome type, cutoff thresholds, and batch effect correction – according to their specific needs. Bulk RNA-seq results are presented in the form of volcano plots, heat-maps, clusters, gene expression across samples, DEGs, and enrichment plots from KEGG and GO analyses. Deconvolution analysis can be performed using either the “LM22” signature matrix (for human leukocyte cell types) or Derm22 (for skin-specific cell types). The single-cell workflow provides results including quality control metrics, UMAP clustering, gene expression plots/tables, and cluster annotation using CellTypist. Comprehensive details on methods and tutorials are available in the GitHub repository. Discussion/Significance of Impact: Although multiple workflows are available to process bulk and single cell RNA-Seq data along with deconvolution methods to bridge the gap between the two, this is the first online interface to provide the capability to explore and analyze data from all three approaches in one place, without requiring strong computational expertise or resources.

OBJECTIVES/GOALS: To identify, categorize, and streamline the wide range of commonly encountered barriers in translational research that prevent studies from progressing along the translational research spectrum through a comprehensive needs assessment survey. Results will be utilized to institute potential solutions to overcome these identified barriers. METHODS/STUDY POPULATION: The comprehensive survey consisted of three sections, Demographics and Background, Self-Reporting of Barriers, and Comments and Feedback. An extensive literature review was conducted to develop and compile questions and barrier categories for the survey. The survey content was derived from primary literature sources and supplemented with the NCATS Translational Science course material. The target population for the survey included all researchers engaged in translational research at the NJ ACTS CTSA hub. The hub includes Rutgers, Princeton, and NJIT and all of their affiliated institutions and partnered healthcare systems, such as Robert Wood Johnson Barnabas Health and University Hospital. Results will be analyzed according to the type of research conducted and stage of translation research (T0-T4). RESULTS/ANTICIPATED RESULTS: Examples of the survey barrier categories being analyzed include Regulatory/IRB, Funding, Collaborations and Networking, and Training. Initial analysis (N=106) consisted of these top barriers in the NJ ACTS CTSA hub: obtaining timely IRB approval, inadequate staffing for the research team, and lack of holistic institutional support. After completion of data collection, the survey results will be further analyzed to determine common barriers and patterns in barrier type across the different institutions, schools, positions/roles in research, and translational research stages. Given that the Comments and Feedback section of the survey entailed ranking the top three barriers across the entire survey as a whole, the results will also indicate the relative prevalence of specific barriers and categories. DISCUSSION/SIGNIFICANCE: The impact of the survey and its results is to develop feasible institutional solutions to overcome the prevalent barriers and improve efficiency in all parts of the research process. Possible solutions encompass accessible resources for researchers, longitudinal training programs, consultative services, and workshops for investigators.

Objectives/Goals: This research aims to harness electronic health records (EHR) combined with machine learning (ML) to predict necrotizing enterocolitis (NEC) in preterm infants using data up to their first 14 days of life. We aim to provide interpretable results for clinical decisions that can reduce infant mortality rates and complications from NEC. Methods/Study Population: Through a retrospective cohort study using data from the University of Florida Integrated Data Repository and One Florida, we will develop machine learning models suitable for sequential data to predict NEC. Our inclusion criteria include very low birth weight (VLBW; <1500g) infants born <32 weeks gestation and EHR data availability from the first 14 days of life. We will include infants with NEC and infants without NEC to train our ML model. Exclusion criteria include infants diagnosed with spontaneous intestinal perforation and severe congenital anomalies/defects requiring surgery. Results/Anticipated Results: We anticipate that our model will provide an accurate and dynamic prediction for the risk of NEC in neonates using data up to the first 14 days of life. Our model will be interpretable to identify key risk factors and can integrate real-world clinical insights to increase early detection and improve patient outcomes. Discussion/Significance of Impact: The development of a model to predict NEC could be used in neonatal intensive care guidelines and protocols and could ultimately decrease mortality, reduce complications, improve the overall quality of care, and lower healthcare costs associated with NEC.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess differences in outcomes between African Americans (AAs) and whites along the HCV care cascade. Primary outcome was retention in the HCV care cascade, measured in two ways. For viral RNA confirmation, retention was a percentage of those having screened antibody reactive. For hepatic ultrasound, primary care, HCV specialty clinic, treatment initiation, and sustained viral load (SVR), retention was a percentage of those found chronically infected by positive RNA viral load. Secondary outcome was time to follow-up from antibody screening to each subsequent step in the care cascade. METHODS/STUDY POPULATION: A retrospective cohort study was performed. AA and white patients who tested HCV antibody reactive from March to October 2015 at the University Medical Center (UMC) Emergency Department in New Orleans, LA were included in this study. Outcomes were assessed using the HCV Continuum of Care model, delineating successive stages of care from identification to cure. RESULTS/ANTICIPATED RESULTS: A total of 728 patients screened HCV antibody reactive, including 446 AAs and 282 whites. AAs (53.5 years, SD 10.2) were disproportionately older than whites (46.7 years, SD 11.9) (p <0.001), more likely to be insured (89.2% vs 78.7%, p<0.001), had higher rates of Medicare (28.0% vs 12.1%, p<0.001), and less frequent history of intravenous drug use (IVDU) (32.3% vs 46.1%, p<0.001). For AAs, retention in the treatment cascade was 96.2% for viral RNA confirmation, 50.9% for hepatic ultrasound, 26.8% for primary care, 35.2% for HCV specialty clinic, 14.5% for treatment initiation, and 9.6% for sustained viral response (SVR). Among whites, retention in the treatment cascade was 96.8% for viral RNA confirmation, 37.8% for hepatic ultrasound, 16.1% for primary care, 23.3% for HCV specialty clinic, 8.8% for treatment initiation, and 7.8% for SVR. AAs had a higher likelihood of receiving a hepatic ultrasound (OR=1.70; CI=1.19-2.25; p<0.005), following up with primary care (OR = 1.91, CI=1.21-3.02, p<0.005), and attending the viral hepatitis specialty clinic (OR=1.79, CI=1.20-2.68, p<0.005), as compared to their white counterparts. After adjusting for age, insurance, and history of IVDU, AAs did not have a higher likelihood of receiving a hepatic ultrasound (aOR=1.09, CI=0.995-1.19) or seeking primary care (aOR=1.05, CI=0.98-1.14). AAs had attenuated odds of attending viral hepatitis specialty clinic (aOR=1.09, CI = 1.01-1.19). There was no statistically significant difference in follow-up time in the treatment cascade for AAs versus whites. DISCUSSION/SIGNIFICANCE OF IMPACT: Race alone cannot explain differences in achievement along the care cascade. Significant differences in retention along the HCV care cascade appear to be related primarily to differences in age and insurance status. In our population, older AAs are disproportionately insured through Medicare, thereby expanding their access to health resources. Their white counterparts are younger and more uninsured, leading to decreased access to care and ability to attend HCV follow-up appointments. ED HCV screening programs are still in their infancy and have opportunities to improve their linkage to care rates. Additional interventions are needed to better connect patients screened positive in the ED to HCV specialist care, preserving equity across racial groups.

ABSTRACT IMPACT: Effective robotic pedaling therapy would allow stroke survivors a precision, customized, and adaptable therapy to help recover lower extremity function. OBJECTIVES/GOALS: It has been observed that people post-stroke can pedal each limb individually but not simultaneously when the bicycle is split-crank. This implies that lower extremity movement difficulties are affected more by interlimb rather than unilateral coordination deficits. This work seeks to further develop a robotic split-crank pedaling therapy device. METHODS/STUDY POPULATION: This work uses a robotic split-crank pedaling device to facilitate rehabilitation of interlimb coordination, measured by continuous relative phase (CRP) and paretic neuromuscular output. The effects of three control schemes were tested: assist, resist, and assist+resist. Each limb was strapped to a pedal which was connected to a motor. The participants were asked to pedal forward while keeping the pedals antiphase. The robot aided or resisted according to the activated control scheme. Control schemes were tested on two stroke participants. The control schemes respond proportionally to phasing deviation from 180 degrees. The assist scheme assisted the lagging limb while the resist scheme resisted the leading limb. The assist+resist did both control actions. RESULTS/ANTICIPATED RESULTS: For the assist scheme, CRP improved for participant 1 (P1) and declined for participant 2 (P2). P1 increased paretic velocity while P2 decreased. Rectus Femoris (RF) and Biceps Femoris (BF) activity of both limbs lowered for P1. RF and BF activity of both limbs remained about the same but shifted for P2. For the resist scheme, CRP improved for P1 and declined for P2. P1 increased paretic velocity while P2 decreased. P1 increased BF activity of both limbs while RF activity remained constant. P2 increased paretic BF activity and non-paretic RF activity. For the assist+resist scheme, CRP improved for both participants. Both participants increased paretic velocity. P1 increased paretic BF activity and decreased RF activity. P2 better modulated paretic BF and RF. DISCUSSION/SIGNIFICANCE OF FINDINGS: All control schemes augmented performance, however the assist+resist scheme showed the most promise in terms of CRP and muscle activity. More participants are needed to determine true effects of each control scheme. The control scheme selected will be the foundation for further improvements such as adaptive control and extrinsic feedback.

OBJECTIVES/GOALS: Burst suppression is a neurophysiological marker associated with severe hypoxic-ischemic injury following cardiac arrest. The goal of this study is to identify the anatomical regions of the brain associated with burst suppression post-cardiac arrest. METHODS/STUDY POPULATION: 86 comatose patients post-cardiac arrest admitted to the neurological-ICU from Massachusetts General Hospital and Brigham and Women’s Hospital were included in this study. EEG data after return of spontaneous circulation were preprocessed and artifact was rejected. Burst segments were extracted for source localization analysis from epochs with burst suppression. Four bursts for each patients were manually selected. The source of the bursts were obtained using the Champagne algorithm and mapped on the Desikan-Killiany atlas. The source for each burst was defined as any region of interest (ROI) with power > = 75th percentile relative to all ROIs. The power of the bursts at each source was correlated with the burden of brain injury measured using apparent diffusion coefficient (ADC) per ROI. RESULTS/ANTICIPATED RESULTS: 48 (56%) patients had burst suppression. 5 (10.4%) of patients with burst suppression were independent at the time of hospital discharge. Preliminary analyses was performed on 6 patients (24 bursts in total). ROI’s determined to be sources in a majority of the burst (>=13) were bilateral superior frontal, rostral middle frontal, parstriangularis precentral, superior parietal, inferior parietal, right post central, superior temporal, lateral occipital, and left middle temporal ROI. A lower mean ADC intensity was associated with a higher EEG power in the bilateral superior frontal (r = -0.80, p < 0.0001; r = -0.677, p < 0.001, respectively), left superior parietal (r = -0.53, p = 0.009), left middle temporal (r = -0.43, p = 0.042) ROI. DISCUSSION/SIGNIFICANCE: The source of bursts in patients post-cardiac arrest experiencing burst suppression is not well defined. This study will improve our understanding of how burst suppression is a measure of cortical injury, how it may relate to the burden of injury found on ADC imaging, and patient outcomes.

OBJECTIVES/GOALS: This team science pilot program aims to elevate the quality of Parkinson’s disease modeling initiatives by strengthening connections between clinical researchers and computational teams. As many data science projects in Parkinson’s research would benefit from deeper clinical expertise, many clinical engagements would be improved by upfront integration of computational requirements. These team science programs, developed from design thinking methodologies, provide structured, sustainable, and scalable means for multi-disciplinary teams to come together and co-create translational science in PD. METHODS/STUDY POPULATION: Design Thinking (DT) could help yield an effective learning experience. DT is grounded in ethnographic research strategies and prototyping, relying heavily on grantee interviews and feedback. This approach is commonly used to navigate and design amidst complexity; its applications range from product to healthcare to instructional design. The following is an overview of the process as applied to this project: Discover: Once the core team (MJFF and project designers) has refined the key question they would like to answer, the team will begin gathering both primary and secondary data. This phase may include focus groups, one-on-one interviews, expert interviews, and immersive data-gathering. The purpose of this phase is to capture complexity and lay the groundwork to understand grantees’ perspectives and lexicon around their work. The deliverables of this phase are primarily unstructured research findings, such as transcribed interviews and secondary sources. Define: When sufficient data has been gathered, the core team will move into an initial round of synthesis and sense-making (making connections and assumptions to explain emerging themes in the data). This phase may include one to two in-person engagements with the core team. The purpose of this phase is to define the guiding principles for subsequent prototypes. It will also help reveal potential opportunity areas, both latent or apparent. The deliverables of this phase are agreed upon key themes, insights, and an informed “How Might We” question that will anchor the ideation process. Develop: Armed with informed themes, the core team will begin to brainstorm potential solutions. Following a set of brainstorming techniques, they will initially aim for quantity versus quality in order to allow potentially innovative and/or risky solutions to surface. Eventually, these ideas will be distilled into three robust and unique prototypes. Like the prior phase, ideation may also require one to two in-person engagements. The deliverables here are three unique prototypes; the reason for three is the ensure that the team does not anchor themselves in just one solution, but rather remains in an exploratory mindset as they solicit feedback on these prototypes from the grantees. Deliver: In this final phase, the core team revisits the grantees and presents the three prototypes. This phase may include conducting three small-scale pilots or simply just explaining the prototypes. Either way, it is important to solicit another round of feedback to ensure the solutions are indeed addressing the needs and context of grantees. Once completed, the core team will iterate a final pilot design and identify any remaining questions and assumptions they would like the pilot to inform. RESULTS/ANTICIPATED RESULTS: The team science pilot identifies five main opportunities to tighten collaboration, communication, and expectations across clinical and computational teams. Firstly, in-person events, held regularly in a central location, can act as an incubating space for these teams to partner, ideate, and pitch for grant funding. Secondly, co-developed guidelines for research questions would ensure consistent availability of clinically-relevant, computationally-feasible research topics. Thirdly, increasing the presence of Parkinson’s cohort data resources at computational conferences could introduce more diverse data and genetics interest in Parkinson’s research. Fourthly, a standard suite of research-facing, educational content (focused on both disease background and data basics) would ensure a strong baseline and launch-pad for PD modeling projects. Lastly, a fellowship program focused on early-stage researchers could establish a unique foundation to ground both clinical and computations fellows to collaboratively work on PD research as well as iterate on the aforementioned solutions. DISCUSSION/SIGNIFICANCE OF IMPACT: This team science program has the potential to upend collaborative silos in Parkinson’s research, accelerating disease modeling projects which otherwise stagnate or over-emphasize clinical v. computational aspects. By more effectively connecting team members with diverse backgrounds across clinical and computational roles, PD disease patterns can be discovered and validated ultimately resulting in improved patient care and therapeutic development. CONFLICT OF INTEREST DESCRIPTION: Several authors are staff members at The Michael J. Fox Foundation for Parkinson’s Research, the sponsor of this Team Science grant. All author and non-author contributors are grant recipients from The Michael J. Fox Foundation.

As part of their mission, Clinical and Translational Science Award (CTSA) hubs are charged with developing, testing, and disseminating evidence-based practices to other CTSA hubs. Over the past 7 years, the University of Wisconsin-Madison has answered this charge by implementing the facilitator training (FT) initiative for research mentors. Three elements to advance training across the CTSA hubs have been critical: (1) using an FT model to empower others to build research mentor training at their local institutions; (2) tracking implementation of training events across the CTSA hubs over time; and (3) partnering with implementation sites to build local capacity and evaluate the effectiveness and quality of training. Here we report that facilitators have been trained at 75% of CTSA hubs. These facilitators report high satisfaction with the training and increased confidence in their ability to implement mentor training, and plan to implement local mentor training. These findings demonstrate that the FT initiative can serve as a model for dissemination and implementation of other workforce development interventions across the CTSA hubs.